In order to accomplish our goals as defined above, we have developed and submitted a clinical protocol to provide access to patient populations and to explore their immune deficits with regards to the oral cavity and/or alternations in the oral microbiome. This protocol is a natural history study designed to investigate the clinical, microbiologic and immunologic consequences of immune dysfunction (particularly due to primary immune defects) in the oral cavity. The hypothesis is that systemic immune dysfunction most commonly attributed to monogenic immune defects in most of our populations of interest, will lead to alterations in the local immune response and microbial colonization and ultimately predispose to susceptibility to oral infections and inflammatory conditions. Of particular interest to this protocol is the susceptibility of select patient populations with immune dysfunction to periodontal disease. For inclusion, subjects must have a current diagnosis of an immune defect (primary or acquired). Subjects will undergo evaluations that include intraoral clinical evaluation, radiographs and sampling for oral fluids, microbes and possibly tissue and blood. Enrolled subjects may be followed up to 3 years to undergo additional clinical evaluation and sampling. Systemically healthy volunteers will be screened and classified as with/without periodontitis. Healthy volunteers will be clinically evaluated and enrolled for a single visit at which they will undergo oral fluid/microbe/tissue/blood sampling for research purposes. The aim of this protocol is to use modern methodologies to characterize the immune response and microbial colonization in the oral cavity in health and disease. By studying particularly subjects with monogenic immune defects we aim to aid in the understanding of the role of specific immune molecules and pathways in the balance of host/microbial interactions on mucosal surfaces such as the oral cavity.